The long-term objective of the proposed program is to obtain a more accurate quantitative estimate of the hazard to human health posed by the presence of heavy metals in our environment. This objective will be attained by studying dose-response relationships in exposed populations, the kinetic parameters describing the uptake, distribution and excretion of heavy metals in humans and by tracing the biological effects at all levels from the whole animal to sub-cellular molecular targets. The methods employed in this program call upon a broad range of disciplines and specialists. Central resources for the program include an analytical laboratory, an archive for the large number of epidemiologic samples, and relevant data processing and retrieval facilities.